There is a significant probability that in the next decade there will be either an influenza (flu) pandemic, a major epidemic of a novel respiratory virus (RV) [e.g., SARS], or a bioterrorism attack that results in respiratory symptoms. In addition, as many as 500,000 people die each year of flu and there is no method to clinically distinguish flu from the many other common RV infections. There is an urgent need for sensitive, highly specific, inexpensive, portable, low complexity devices/assays that allow for the multiplex detection and identification of flu and other common RV's. We have a long record of developing multiplex commercial assays for flu and other RVs and developed the first commercial multiplex molecular assay for flu A, B, RSV A, B, and parainflu 1,2,3 in the world (Hexaplex, 1996) and the first assay for SARS in the US (2003). We have now developed novel fully integrated technology based on a unique sample collection device (SCD), stable europium fluorescent microparticles (EFM), and binding chemistry based on pRNA that allows for sensitive (400x >than FDA approved assays) bedside or in-the-field multiplex POC antigen testing of patients. This technology runs on batteries, takes 15 minutes, and can detect multiple viruses simultaneously. Even more importantly the SCD collects and stabilizes a sample of nucleic acid (RNA and DNA) for use in molecular assays as needed (allowing for testing of negative samples or further analysis of positives while maintaining biocontainment). In this application we propose the following specific aims:! Select and optimize the chemistry, substrate, and hardware to produce a SCD-EFM-pRNA assay to detect 13 common RV's causing LRI or significant disease in children and adults (flu A, B, RSV, [paraflu 1,2,3, hMPV], corona- viruses [NL63, HKU1, 229E, OC43], adenovirus, and enterovirus). 2. Develop a multiplex-RT-PCR electronic microarray (eMR) assay to these same 13 viruses as a confirmatory molecular assay (also as a product), determine and compare analytical LOD, sensitivity and specificity with multiplex immunoassay developed in SA 1 and other established molecular assays. 3. Determine optimal parameters required by FDA. (e.g., ensure design of all components, ease of use guidelines, and results interpretation by non-professional laboratory personnel meets CLIA waived standards for assay in SA#1);4. Process Development (methods to ensure manufacturability of the diagnostic components and commercialization at a reasonable cost). 5. Clinical sample testing (frozen samples);To determine if the multiplex POC assays developed in SA#1 &2 to the majority of RV that produce "Flu-like" symptoms and LRI can demonstrate improved clinical sensitivity, specificity, and cost effectiveness compared to currently available standard diagnostic assays. After completion of these SAs, clinicians and public health officials will have two important new tools to fight flu and viral respiratory infections, whether from their hospital, office or the most remote locations on the planet.